1. Maria Victoria B. Pertubal, M.D. PGY1
Neonatal sepsis
Maria Victoria B. Pertubal, M.D.
PGY1

2. Etiology & Pathogenesis Evaluation and Diagnosis
Definition of terms
Epidemiology
Etiology & Pathogenesis
Evaluation and Diagnosis
Clinical Manifestations
Laboratory
Management Algorithm of NB sepsis
Treatment options
Preventive management

3. Definition of terms Neonatal period Neonatal sepsis
first month / 28 days of life
Neonatal sepsis
clinical syndrome in an infant 28 days of life or younger, manifested by systemic signs of infection and/or isolation of a bacterial pathogen from the blood stream

4. Early-onset vs. Late-onset sepsis
Definition of terms
Early-onset vs. Late-onset sepsis
Onset of symptoms
72 hours or ≥7 days of age

5. Definition of terms Intrapartum period
(NSVD) - from onset of labor / ROM to delivery
(CS) - between admission for labor and cord clamping

6. How common is it and who are at risk?

7. EPIDEMIOLOGY / RISK FACTORS
Overall incidence
1-5 cases per 1000 live births
Preterm vs. Full term
GBS sepsis blacks>whites
asphyxia, meconium stained AF
Disrupted skin & mucosal integrity
(IV catheter)
Environmental exposure / direct contact

8. Maternal RISK FACTORS Socioeconomic Infectious : Obstetrical:
SE status, poor prenatal care, maternal substance abuse
Infectious :
Chorioamnionitis, fever (>38° C/100.4° F), venereal diseases, UTI/bacteriuria, GBS+
Obstetrical:
amniocentesis, amnioinfusion, prolonged labor, PPROM, preterm labor

9. Incidence of early- and late-onset invasive group B streptococcal (GBS) disease: Active Bacterial Core surveillance areas, *, and activities for prevention of GBS disease
ACOG: American College of Obstetricians and Gynecologists; AAP: American Academy of Pediatrics. * Incidence rates for 2008 are preliminary because the live birth denominator has not been finalized.
Reproduced from: Verani, JR, McGee, L, Schrag, SJ, et al. Prevention of perinatal group B streptococcal disease--revised guidelines from CDC, MMWR Recomm Rep 2010; 59(RR-10):1. Original data from: Jordan, HT, Farley, MM, Craig, A, et al. Revisiting the need for vaccine prevention of late-onset neonatal group B streptococcal disease: a multistate, population-based analysis. Pediatr Infect Dis J 2008; 27:1057.

10. How is neonatal infection acquired?

11. Routes of Infection Vertical Transplacental Viruses > Bacterial
TORCHES
HIV Coxsackie Polio
Adenovirus EchoEnterovirus
Varicella Parvovirus*
TB Gonorrhea
Malaria Lyme
Vertical
Bacterial >Viral
(maternal)
GBS E. Coli
Listeria Anaerobes
Enterococcus
Chlamydia Gonorrhea
Ureaplasma Mycoplasma
Syphilis
Herpes HIV Hepatitis HPV
Candida
Horizontal
Bacterial
(nosocomial/
Environmental)
Klebsiella
Staphylococcus –MRSA
Pseudomonas Proteus
Enterobacter
Serratia C dificile
Rotavirus Fungi

13. Group B Streptococcus aka. Streptococcus agalactiae
Serotype distribution — corresponds to the capsular polysaccharide.
9 serotypes: Ia, Ib, and II through VIII; serotype IX has been proposed
Serotypes Ia, Ib, II, III, and V account for more than 95 percent of early-onset cases in the United States and more than 90 percent of late-onset cases
Serotype III – meningitis; high proportion of late-onset infections
The distribution of serotypes and surface proteins among GBS isolates has important implications for the development of vaccines to prevent GBS disease.

14. Pathways of ascending or intrapartum infection
Pathways of ascending or intrapartum infection. (Figure Nelson Pediatrics)

15. Early onset sepsis is most commonly due to: A) Vertical / ascending transmission B) Horizontal transmission?

16. How do we RECOGNIZE and DIAGNOSE sepsis?

17. INITIAL SIGNS AND SYMPTOMS OF INFECTION IN NEWBORN INFANTS
 GENERAL  
Fever, temperature instability
“Not doing well”  Poor feeding   Edema
RESPIRATORY SYSTEM  
Apnea, dyspnea, Tachypnea, retractions, Flaring, grunting, Cyanosis
CARDIOVASCULAR SYSTEM 
 Pallor; mottling; cold, clammy skin Tachycardia Hypotension   Bradycardia
RENAL SYSTEM  
Oliguria
GASTROINTESTINAL SYSTEM  
Abdominal distention   Vomiting, Diarrhea, Hepatomegaly
HEMATOLOGIC SYSTEM  
Jaundice, Splenomegaly, Pallor, Petechiae, purpura, Bleeding
CENTRAL NERVOUS SYSTEM  
Irritability, lethargy, Tremors, seizures, Hyporeflexia, hypotonia, Abnormal Moro reflex, Irregular respirations, Full fontanel, High-pitched cry
Kliegman: Nelson Textbook of Pediatrics, 19th ed.
Copyright © 2011 Saunders, An Imprint of Elsevier

18. History Review of the pregnancy, labor, and delivery Duration
Mode of delivery
Newborn condition at delivery (APGAR & BW)

19. Maternal-Neonatal Risk factors for sepsis
Intrapartum maternal temperature ≥38ºC (100.4ºF)
Delivery at <37 weeks gestation
Chorioamnionitis
Five minute Apgar score ≤6 Evidence of fetal distress
Membrane rupture ≥18 hours
risk of proven sepsis increases 10 fold to 1 %
Maternal GBS colonization
Use of Intrapartum antibiotic prophylaxis (IAP)

21. differential diagnosis
other systemic bacterial infections,
neonatal hypoxia,
in-born errors of metabolism,
neonatal respiratory distress.

22. What LABORATORY exams will you request?

23. Laboratory BLOOD TESTS:
Blood culture establishes a definitive diagnosis
Other blood tests:
CBC – within 24h
Immature to total PMN ratio (I:T ratio)
Inflammatory markers:
CRP, cytokines, procalcitonin (released by parenchymal cells in response to bacterial toxins

24. Laboratory Urine : Culture – for all infants older than 3 days of age
If done on younger infants, it may only reflect high grade bacteremia rather than isolated UTI

25. Other ancillary Chest X-ray
If with clinical signs of RDS
Cultures from other potential foci of infection
Secretions/pus

26. Laboratory BLOOD TESTS:
Blood culture establishes a definitive diagnosis
Other blood tests:
CBC – within 24h
Immature to total PMN ratio (I:T ratio)
Inflammatory markers:
CRP, cytokines, procalcitonin (released by parenchymal cells in response to bacterial toxins

27. Laboratory CSF analysis:
should be considered in all neonates; clinical signs of meningitis can be lacking in young infants
Send for :
Culture
gram stain,
cell count
protein
glucose

28. Bacterial meningitis CSF findings
Culture
Gram
stain
WBC
protein
glucose
Can be negative in 30-38% of
20 percent of neonates with culture-confirmed bacterial meningitis have negative Gram-stained
>20 to 30 cells/
microL
>1000
*greater count in Gneg meningitis
preterm >150 mg/dL
term >100 mg/dL in
preterm <20 mg/dL
(1.1 mmol/L)
term
<30 mg/dL
(1.7 mmol/L)

29. What is our Management GOAL?
Be HIGHLY suspicious of all potential neonatal sepsis cases

30. Algorithm for secondary prevention of early-onset group B streptococcal (GBS) disease among newborns
Full diagnostic evaluation :
blood culture,
complete blood count (CBC) w/ differential and platelet counts,
chest radiograph (if respiratory abnormalities are present),
lumbar puncture (if patient is stable enough to tolerate procedure and sepsis is suspected).
† Antibiotic therapy - directed toward the most common causes of neonatal sepsis,
intravenous ampicillin for GBS
and coverage for other organisms (including Escherichia coli and other gram-negative pathogens) -must take into account local antibiotic resistance patterns.

31. § Consultation with obstetric providers is important to determine the level of clinical suspicion for chorioamnionitis. Chorioamnionitis is diagnosed clinically and some of the signs are nonspecific.
¶ Limited evaluation
blood culture (at birth)
CBC with differential and platelets (at birth and/or at 6–12 hours of life).

32. ** See indications for intrapartum GBS prophylaxis.
†† If signs of sepsis develop:
Conduct full diagnostic evaluation
Initiate antibiotic therapy

34. §§ observation may occur at home
If ≥37 weeks’ gestation, after 24 hours if other discharge criteria have been met
access to medical care is readily available,
person who is able to comply fully for home instruction will be present.
If any of these conditions is not met, the infant should be observed in the hospital for at least 48 hours and until discharge criteria are achieved.

35. For LOW RISK
¶¶ Some experts recommend a CBC with differential and platelets at age 6–12 hours.

36. ¶ Limited evaluation
blood culture (at birth)
CBC with differential and platelets (at birth and/or at 6–12 hours of life).

39. What is the value of antenatal screening for GBS?

40. Year 2002
Universal screening at weeks' gestation for maternal GBS colonization and use of intrapartum antibiotic prophylaxis has resulted in substantial reductions in the burden of early-onset GBS disease among newborns.

41. Incidence of early- and late-onset invasive group B streptococcal (GBS) disease: Active Bacterial Core surveillance areas, *, and activities for prevention of GBS disease
ACOG: American College of Obstetricians and Gynecologists; AAP: American Academy of Pediatrics. * Incidence rates for 2008 are preliminary because the live birth denominator has not been finalized.
Reproduced from: Verani, JR, McGee, L, Schrag, SJ, et al. Prevention of perinatal group B streptococcal disease--revised guidelines from CDC, MMWR Recomm Rep 2010; 59(RR-10):1. Original data from: Jordan, HT, Farley, MM, Craig, A, et al. Revisiting the need for vaccine prevention of late-onset neonatal group B streptococcal disease: a multistate, population-based analysis. Pediatr Infect Dis J 2008; 27:1057.

43. Recommended regimens for intrapartum antibiotic prophylaxis for prevention of early-onset group B streptococcal (GBS) disease*

44. Algorithm for screening for GBS colonization and use of intrapartum prophylaxis for women with preterm* labor (PTL)

45. SUMMARY
Neonatal sepsis is is classified by the infant's age into early-onset sepsis (≤3 to 7 days) and late-onset sepsis (>3 or 7 to 28 days).
Group B Streptococcus (GBS) and Escherichia coli are the most common bacteria causing neonatal sepsis
Risk factors for neonatal sepsis in term and late preterm infants include intrapartum maternal temperature ≥38ºC (100.4ºF), chorioamnionitis, five minute Apgar score ≤6, maternal GBS colonization, and membrane rupture ≥18 hours.

46. SUMMARY
Evaluation include a prenatal history, delivery, complete physical examination, and a laboratory evaluation that minimally includes a blood culture.
overall incidence of early onset GBS disease in NB substantially decreased over the last decade with universal screening for maternal GBS and use of IAP
Initial empirical antibiotic therapy for suspected GBS disease should include broad coverage for the most likely pathogens (Ampicillin/Vancomycin-Gentamicin/Cefotaxime)

47. any deviation from an infant's usual pattern of activity or feeding should be regarded as a possible indication of systemic bacterial infection
Nizet, V, Klein, JO. Bacterial sepsis and meningitis. In: Infectious diseases of the Fetus and Newborn Infant, 7th ed, Remington JS et al (Ed), Elsevier Saunders, Philadelphia p.222.

48. SUMMARY
Routine hand hygiene by health care professionals is the best way to prevent health care-associated spread of GBS infection

49. Salamat po 